| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| ln Vitro |
AM 103's IC50 result in a human blood LTB4 inhibition test was 349 nM. When it comes to the five most prevalent CYP isoforms, AM 103 has good CYP characteristics; its IC50 values for CYP2D6 are greater than 30 μM, while those for CYP 3A4, 2C9, 2C19, and 1A2 are greater than 50 μM [1]. With IC50 values of 350, 113, and 117 nM for ionophore-stimulated LTB4 in human, rat, and mouse whole blood, respectively, AM103 is a new, powerful, and specific FLAP inhibitor [2].
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| ln Vivo |
In dogs, AM 103 exhibits a long intravenous half-life (5.2 h), low clearance (2.9 mL/min/kg), modest volume of distribution (0.41 L/kg), and excellent bioavailability (64%). AM 103 (10 mg/kg qd) lowers IL-5 levels to the levels attained after administering saline alone to mice, and it suppresses the rise in CysLT and EPO by around 60% [1]. With an estimated EC50 of about 60 nM, AM103 (1 mg/kg, po) demonstrated >50% inhibition for up to 6 hours in an ex vivo rat whole blood calcium ionophore-induced LTB4 test. AM 103 reduced the synthesis of cysteinyl leukotriene (CysLT) and LTB4 in rat lungs when they were exposed to calcium ionophores in vivo, with ED50 values of 0.8 and 1 mg/kg, respectively. With an EC50 of about 330 nM, AM103 from plasma inhibits LTB4 and CysLT in this model. AM103 decreased the levels of eosinophil peroxidase, CysLT, and interleukin-5 in bronchoalveolar lavage fluid in a model of chronic lung inflammation in BALB/c mice primed and challenged with ovalbumin. Lastly, animals given deadly intravenous doses of platelet-activating factor have longer life times when AM 103 is administered [2].
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Well absorbed orally. |
| References |
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| Additional Infomation |
AM103 is a novel inhibitor of 5-lipoxygenase-activiting protein (FLAP) that has demonstrated potential to treat asthma and cardiovascular disease by preventing the synthesis of LT, which triggers inflammation. It is being developed by Amira.
Drug Indication For the treatment of asthma and cardiovascular disease. Mechanism of Action The exact mechanism of actions is not known, however, AM103 inhibits the 5-lipoxygenase-activiting protein (FLAP). This prevents the synthesis of LT, which normally triggers inflammation. Pharmacodynamics Results from the Phase I trial show that AM103 is safe and well-tolerated at doses up to 1,000 mg per day with no evidence of significant side effects. Pharmacodynamic data demonstrated a robust and statistically significant reduction of LTB4 and LTE4 in a dose-dependent manner. |
| Molecular Formula |
C36H38N3NAO4S
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|---|---|
| Molecular Weight |
631.759398937225
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| Exact Mass |
631.248
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| CAS # |
1147872-22-7
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| PubChem CID |
59248882
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
6.943
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
45
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| Complexity |
927
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
NJJMCCVPHCNMPB-UHFFFAOYSA-M
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| InChi Code |
InChI=1S/C36H39N3O4S.Na/c1-35(2,3)44-33-29-19-28(43-23-27-9-7-8-18-37-27)15-16-30(29)39(31(33)20-36(4,5)34(40)41)22-24-10-12-25(13-11-24)26-14-17-32(42-6)38-21-26;/h7-19,21H,20,22-23H2,1-6H3,(H,40,41);/q;+1/p-1
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| Chemical Name |
sodium;3-[3-tert-butylsulfanyl-1-[[4-(6-methoxypyridin-3-yl)phenyl]methyl]-5-(pyridin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~200 mg/mL (~316.58 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (7.91 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (7.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5829 mL | 7.9144 mL | 15.8288 mL | |
| 5 mM | 0.3166 mL | 1.5829 mL | 3.1658 mL | |
| 10 mM | 0.1583 mL | 0.7914 mL | 1.5829 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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